Abstract
Several non-surgical tumor treatment modalities produce their cytotoxic activity by generating reactive oxygen species (ROS). Anti-oxidative enzymes such as superoxide dismutase (SOD) or exogenously supplied antioxidants may therefore reduce the efficacy of these treatments. The aim of the present study was to analyze the impact of (i) inhibiting SOD using 2-methoxyestradiol (2-ME), or (ii) application of α-tocopherol, on the cellular damage induced by hyperthermia (HT) in experimental tumors. DS-sarcoma cells grew either in culture or as solid tumors subcutaneously implanted in rats. In vitro, DS-cells were incubated with 2-ME, and cell proliferation, ROS formation, lipid peroxidation and apoptosis were measured. In vivo, DS-sarcomas were treated with a ROS-generating hyperthermia combined with 2-ME or α-tocopherol application.
Inhibition of SOD by 2-ME in vitro induced pronounced oxidative injury resulting in reduced proliferation. In vivo, ROS-generating hyperthermia led to local tumor control in 23% of the animals. The additional inhibition of SOD by 2-ME increased the control rate by approximately 50%. Application of α-tocopherol was found to have no effect on local tumor control, either in combination with ROS-generating hyperthermia or when 2-ME was additionally applied. Inhibition of SOD during ROS-generating hyperthermia results in pronounced cell injury and an improved local tumor control whereas exogenously applied vitamin E seems not to have an impact on oxidative stress.
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6. References
E. J. Hall, Radiobiology for the Radiologist, 5th edition (J.B. Lippincott, Philadelphia, 2000).
B. K. Sinha, and E. G. Mimnaugh, Free radicals and anticancer drug resistance: oxygen free radicals in the mechanisms of drug cytotoxicity and resistance by certain tumors, Free Radical Biol. Med. 8, 567–581 (1990).
Q. Chen, Z. Huang, H. Chen, H. Shapiro, J. Beckers, and F. W. Hetzel, Improvement of tumor response by manipulation of tumor oxygenation during photodynamic therapy, Photochem. Photobiol. 76, 197–203 (2002).
I. Fridovich, Superoxide radical and superoxide dismutases, Ann. Rev. Biochem. 64, 97–112 (1995).
P. Huang, L. Feng, E. A. Oldham, M. J. Keating, and W. Plunkett, Superoxide dismutase as a target for the selective killing of cancer cells, Nature 407, 390–395 (2000).
E. Germain, V. Chajes, S. Cognault, C. Lhuillery, and P. Bougnoux, Enhancement of doxorubicin cytotoxicity by polyunsaturated fatty acids in the human breast tumor cell line MDA-MB-231: relationship to lipid peroxidation, Int. J. Cancer 75, 578–583 (1998).
J. Hannemann, and K. Baumann, Cisplatin-induced lipid peroxidation and decrease of gluconeogenesis in rat kidney cortex: different effects of antioxidants and radical scavengers, Toxicology 51, 119–132 (1988).
C. Leonetti, A. Biroccio, C. Gabellini, M. Scarsella, V. Maresca, E. Flori, L. Bove, A. Pace, A. Stoppacciaro, G. Zupi, F. Cognetti, and M. Picardo, α-tocopherol protects against cisplatin-induced toxicity without interfering with antitumor efficacy, Int. J. Cancer 104, 243–250 (2003).
J. Frank, D. K. Kelleher, A. Pompella, O. Thews, H. K. Biesalski, and P. Vaupel, Enhancement of oxidative cell injury and antitumor effects of localized 44°C hyperthermia upon combination with respiratory hyperoxia and xanthine oxidase, Cancer Res. 58, 2693–2698 (1998).
T. Fotsis, Y. Zhang, M. S. Pepper, H. Adlercreutz, R. Montesano, P. P. Nawroth, and L. Schweigerer, The endogenous oestrogen metabolite 2-methoxyoestradiol inhibits angiogenesis and suppresses tumour growth, Nature 368, 237–239 (1994).
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Thews, O., Lambert, C., Kelleher, D.K., Biesalski, HK., Vaupel, P., Frank, J. (2005). Possible Protective Effects of α-Tocopherol on Enhanced Induction of Reactive Oxygen Species by 2-Methoxyestradiol in Tumors. In: Okunieff, P., Williams, J., Chen, Y. (eds) Oxygen Transport to Tissue XXVI. Advances in Experimental Medicine and Biology, vol 566. Springer, Boston, MA. https://doi.org/10.1007/0-387-26206-7_46
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DOI: https://doi.org/10.1007/0-387-26206-7_46
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